Mycobacterium tuberculosis (Mtb) alters the intracellular environment of the alveolar macrophage (M[unreadable]), the primary host cell, allowing bacterial replication within the cell. However virulent Mtb eventually induces necrosis characterized by M[unreadable] lysis facilitating escape of the bacteria and dissemination. To induce necrosis virulent Mtb inhibits apoptosis, which is beneficial to the host leading to death of the pathogens. We showed that following Mtb infection, the balance of the host lipid mediators prostaglandin E2 and lipoxin A4 determines whether infected M[unreadable] undergo necrosis or apoptosis. Virulent Mtb induce production of lipoxin A4, which suppresses prostaglandin E2 production leading to necrosis. In contrast, M[unreadable] infected with avirulent Mtb produce mainly prostaglandin E2 leading to apoptosis. This is accomplished by rapid resealing of Mtb-induced plasma membrane microdisruptions triggered by a lysosome and Golgi vesicle dependent repair mechanism. In contrast, infection with virulent Mtb inhibits membrane repair leading to necrosis. We hypothesize that impairment of membrane repair leads to phagosomal membrane damage, cytosol entry of the bacteria, and necrosis. Following necrosis of the host M[unreadable] Mtb infect other cells to initiate another cycle of replication. We propose to investigate how the lipid mediators regulate membrane repair, how Mtb escapes from the phagosome and whether membrane repair is important to prevent escape and spreading of the bacteria. Better understanding of the events leading to M[unreadable] apoptosis and necrosis of Mtb-infected M[unreadable] will foster our understanding of tuberculosis pathogenesis and will guide research into new therapies.